Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies

Wound Infiltration With Liposomal Bupivacaine With or Without Intrathecal Analgesia in Laparotomy for Gynecological Malignancy: A Randomized Controlled Trial

This phase IV trial studies how well liposomal bupivacaine with or without hydromorphone works in improving pain control during the first 24 hours after surgery in patients with gynecological malignancies undergoing laparotomy. Liposomal bupivacaine is routinely infiltrated into the skin surrounding the abdominal incision, and is effective in providing good relief of incisional pain. Hydromorphone is also a type of pain medication that may provide better management of deep abdominal pain. It is not yet known if giving liposomal bupivacaine with or without hydromorphone will work better in improving pain in patients with gynecological malignancies during the first 24 hours after surgery.

Study Overview

• Status: Completed
• Conditions: Malignant Female Reproductive System Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Laparotomy; Drug: Liposomal Bupivacaine; Drug: Hydromorphone

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate if no additional intervention is noninferior to intrathecal analgesia (ITA) for postoperative pain experience 24 hours after surgery after laparotomy for gynecological malignancy within an established enhanced recovery pathway which includes incisional liposomal bupivacaine (ILB).

II. Evaluate the effect of intrathecal analgesia on patient satisfaction with postoperative analgesia after laparotomy for gynecological malignancy.

III. Report the impact of ITA use on cost. IV. Validate the Quality of Recovery (QOR)-15 in our population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.

ARM II: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone intrathecally (IT).

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Elective surgery for suspected (based on consulting surgeon's opinion-imaging, laboratory [lab], pathology [path]) gynecological malignancy, enhanced recovery after surgery (ERAS) protocol

Exclusion Criteria:

• Inability to read or understand English
• Prehospitalization narcotic use if weekly average daily oral morphine equivalent of > 20 mg
• Chronic pain syndromes such as fibromyalgia
• Extensive surgery planned (surrogate for post-operative [postop] pain): Planned intensive care unit (ICU) admission, abdominoperineal resection, exenteration, use of intraoperative radiation (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC)

• Contraindication to neuraxial analgesia:

  • Coagulopathy

    • International normalized ratio (INR) > 1.2 current or predicted after surgery (e.g. planned right hepatic resection)
    • Thrombocytopenia. Platelets (plts) < 100
    • Hemophiliac disease states (hemophilia, von Willebrand disease, etc.)
    • Patients receiving antithrombotic or thrombolytic therapy are excluded according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines
  • Localized infection at the potential site of injection
  • Significant developmental or structural spinal abnormalities that would preclude a safe spinal technique. These include spina bifida, tethered spinal cord, lumbar spinal fusion, and active lumbar radiculopathy
• Patients with stage 4 or 5 kidney disease (glomerular filtration rate [GFR] less than 30 ml/min per 1.73 m^2)
• Intolerance or allergy to opioids, acetaminophen, or amide-type local anesthetics
• Current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (laparotomy, liposomal bupivacaine); Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.	Other: Questionnaire Administration; Ancillary studies; Procedure: Laparotomy; Undergo laparotomy; Drug: Liposomal Bupivacaine; Drug; Other Names: Exparel; Bupivacaine Liposome Injectable Suspension
Experimental: Arm II (laparotomy, liposomal bupivacaine, hydromorphone); Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.	Other: Questionnaire Administration; Ancillary studies; Procedure: Laparotomy; Undergo laparotomy; Drug: Liposomal Bupivacaine; Drug; Other Names: Exparel; Bupivacaine Liposome Injectable Suspension; Drug: Hydromorphone; Given IT; Other Names: (-)-Hydromorphone; Dihydromorphinone; Hydromorphon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Benefit of Analgesia Score (OBAS)	The mean OBAS score between the two groups will be presented along with the upper limit of the 95% confidence bound for the mean difference. Will conclude non-inferiority if this upper limit is less than the predefined limit for noninferiority. Multivariable regression models will be fit to assess for differences in outcomes if there are unbalanced baseline covariates in the two treatment arms. Each of 7 questions are scored on a scale of 0 - 4 with a lower total score reflecting a better outcome.	Up to 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative 24 hour narcotic consumption	Will be measured in morphine metabolic equivalents. Data will be summarized using standard descriptive statistics by reporting mean (standard deviation [SD]) or median (interquartile range [IQR]) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Post-operative pain scores	Post-operative pain scores, including rest and movement, will be measured at 4, 8, 16 and 24 hours after surgery. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test. Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.	Up to 24 hours after surgery
Time to first analgesic request	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Use of intravenous (IV) patient-controlled analgesia	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Use of intravenous rescue opioids	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Length of stay	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Additional fluid requirement after 24 hours of surgery	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Weight gain following surgery	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Cost of care	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Incidence of adverse events	Incidence of adverse events related to spinal injection, systemic opioid effects and delayed recovery will be assessed. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Operating room time	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Surgical time	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery
Total and pain management related standardized costs	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.	Up to 24 hours after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery-15	Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test. The questionnaire includes 15 items, each scored on a scale of 1 - 10, with a total higher score reflecting better outcomes.	At 24 hours after surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sean C Dowdy, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): May 8, 2023
• Study Completion (Actual): May 8, 2023

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Hydromorphone
• Other Study ID Numbers: MC2061 (Other Identifier: Mayo Clinic in Rochester); NCI-2020-00609 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-010500

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No